Respiratory infections (RIs), a broad term including both upper RIs (e.g., common colds, pharyngitis, and sinusitis) and lower RIs (e.g., pneumonia and bronchitis), are a significant public health challenge associated with high morbidity and mortality worldwide (1, 2). Children and adolescents are particularly susceptible to RIs due to their immature immunity systems, which are further aggravated by the increasing environmental pollution in recent years (3). According to the World Health Organization (WHO), pneumonia caused 740,180 deaths among children aged < 5 years in 2019, accounting for 14% of all deaths in that age group (4). Identifying risk factors, especially those modifiable factors that are easy to intervene, is thus crucial for the prevention and control of RIs among children and adolescents.

Abundant evidence has demonstrated that nutrition plays an essential role in RIs among children and adolescents, as poor nutritional status can lead to impaired immunity, thus increasing their susceptibility to RIs (5). Vitamin C is a vital type of micronutrient with anti-inflammatory, antioxidant, and immune-modulating properties (6). It can improve immunity by supporting epithelial barrier integrity, enhancing immune cell activity, and alleviating oxidative stress (7). A multitude of observational studies have indicated a significant association between the level of vitamin C and the risk of RIs, particularly among older adults and people with immune dysfunction (8, 9). In addition, several meta-analyses of randomized controlled trials (RCTs) from global research indicate that vitamin C supplementation can effectively prevent RIs and significantly reduce the duration of RIs (10–12).

However, the relationship between vitamin C and RIs focusing on the younger population who are disproportionally affected by a high disease burden of RIs remains less studied and reported (13). High-quality evidence based on large population studies on the association between vitamin C and RIs in the context of children and adolescents is even scarce. Therefore, this study aimed to evaluate the relationship between serum vitamin C and RIs in a representative sample of children and adolescents from the National Health and Nutrition Examination Survey (NHANES). Our findings would offer comprehensive insights into the impact of nutritional factors on respiratory health in children, providing a basis for developing effective preventive and intervention strategies.

This was the first population-based study examining the association between serum vitamin C levels and RIs in US children. After adjusting for demographic and health characteristics, we found that a higher level of serum vitamin C was associated with a lower risk of RIs. Subgroup analyses further substantiated this association, demonstrating its robustness and resistance to influence by confounding variables such as sex, age, family PIR, BMI, asthma, or tobacco smoke exposure. Our findings highlight the protective role of vitamin C against RIs, which may provide useful guidance for future prevention and treatment of RIs among children.

The finding that higher serum vitamin C was associated with a RI risk in children and adolescents was consistent with previous studies in other countries. A survey conducted in the United Kingdom involving 19,357 adults found an inverse relationship between vitamin C and the risk of RIs (20). A study conducted in Italy, which involved 60 children, found that supplementing vitamin C in children significantly decreased the incidence of recurrent RIs (21). A similar finding was reported in a study conducted among 69 preschool children in Slovakia, which demonstrated that combining vitamin C and probiotics significantly decreased the incidence of upper RIs and the use of antibiotics and cough medications (22). Our study added further evidence on the beneficial effects of vitamin C in RI prevention and control, which could inform future research and clinical applications.

The underlying mechanisms of the beneficial role of vitamin C on RIs primarily involve its antioxidant, immune-modulatory, and anti-inflammatory properties. Research indicates that vitamin C protects against RIs through several mechanisms. First, vitamin C exerts antioxidant functions by neutralizing free radicals, mitigating oxidative stress, and protecting the integrity of respiratory epithelial cells (7). Second, vitamin C strengthens immunity by enhancing the chemotaxis and phagocytic activity of neutrophils, which is essential for pathogen clearance (23). Third, vitamin C exerts anti-inflammatory functions by modulating cytokine production and inhibiting pro-inflammatory cytokines (e.g., TNF-αand IL-6), thereby reducing inflammatory responses (24). Fourth, our previous research has demonstrated a negative correlation between serum vitamin C and C-reactive protein (CRP), an important inflammatory marker, in children (13). Vitamin C can reduce pulmonary inflammation, improve respiratory function, and shorten the duration of the RIs through its anti-inflammatory functions (25).

On the other hand, vitamin C deficiency can increase the risk of RIs. Previous studies have observed lower levels of vitamin C in hospitalized patients with RIs, probably due to increased metabolic demands (26). In addition, patients with lower vitamin C levels exhibit more severe symptoms and longer recovery duration during infections (27). In critically ill patients, intravenous supplementation of vitamin C can reduce the length of hospitalization and improve survival (28). Consequently, ensuring adequate vitamin C supplementation holds potential clinical significance in the management of RIs, particularly among vulnerable populations, such as older adults and immunocompromised individuals (29). In our study, maintaining higher serum vitamin C concentrations was crucial in preventing RIs in children and adolescents.

The present study boasts several strengths. First, participants were recruited from the 2017–2018 NHANES, ensuring the sample representativeness. Second, the analysis was adjusted for multiple potential confounders, enhancing the reliability of the findings. Third, the results were tested among various subgroups, confirming the stability of the association. However, the study has several limitations. First, the sample was recruited from a US population and may not represent children in other countries. Future studies in other nations are needed to validate our findings in other populations. Second, the cross-sectional study design cannot establish causal references, indicating the need for future longitudinal study designs. Third, although we adjusted for multiple confounders, there may be other unmeasured potential confounding factors that affect the results. For instance, we did not account for other drugs that may influence vitamin C absorption, depletion, or demand, which may make it difficult to determine the true effect of vitamin C in our study. Future research should address potential drug interactions to provide more accurate and reliable conclusions about the role of vitamin C in RIs. Fourth, RIs were determined based on two self-reported questions, which may introduce potential information and recall bias. Future studies should consider using more robust assessment approaches, such as medical records, physical examinations, and laboratory tests to get a more accurate evaluation. Fifth, while our study showed that lower vitamin C levels were associated with a higher risk of RIs, it should be noted that RIs may also lead to lower vitamin C levels due to the increased demands of the immune system during the infection response. Future research should consider exploring the bidirectional relationship between vitamin C levels and RIs and their underlying mechanism, offering a more nuanced understanding of their interactions. Finally, we did not account for other health conditions that may impair vitamin C absorption or metabolism. Conditions like irritable bowel disease (IBD), celiac disease, and chronic infections can all contribute to vitamin C deficiency through various ways, including reduced nutrient intake, increased nutrient losses, and impaired absorption. Future research should consider and control for these factors to improve the accuracy and relevance of findings.

This study demonstrates a negative association between serum vitamin C and RI risk in a nationally representative sample of children and adolescents. These findings highlight the protective role of vitamin C against RIs and underscore the significance of maintaining optimal vitamin C levels. Our findings suggest that vitamin C supplementation may be potentially used for the prevention and treatment of RIs among children and adolescents, which needs to be further validated in future well-designed studies.